rs17293632

Variant names:

• chr15-67150258-C-T
• rs17293632
• NM_005902.4:c.207-14637C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-67150258-C-T
• chr15-67150258-C-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The NM_005902.4(SMAD3):​c.207-14637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,144 control chromosomes in the GnomAD database, including 2,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2806 hom., cov: 32)
• Consequence: SMAD3 NM_005902.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86
• Publications: 162 publications found

Genes affected

SMAD3 (HGNC:6769): (SMAD family member 3) The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]

SMAD3 Gene-Disease associations (from GenCC):

• aneurysm-osteoarthritis syndrome

  Inheritance: Unknown, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 15-67150258-C-T is Benign according to our data. Variant chr15-67150258-C-T is described in ClinVar as Benign. ClinVar VariationId is 811543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD3	NM_005902.4	MANE Select	c.207-14637C>T		intron	N/A	NP_005893.1	P84022-1
	SMAD3	NM_001407011.1		c.207-14637C>T		intron	N/A	NP_001393940.1	H3BQ00
	SMAD3	NM_001145103.2		c.74+12158C>T		intron	N/A	NP_001138575.1	P84022-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAD3	ENST00000327367.9	TSL:1 MANE Select	c.207-14637C>T		intron	N/A	ENSP00000332973.4	P84022-1
	SMAD3	ENST00000439724.7	TSL:1	c.74+12158C>T		intron	N/A	ENSP00000401133.3	P84022-2
	SMAD3	ENST00000540846.6	TSL:1	c.-109-14637C>T		intron	N/A	ENSP00000437757.2	P84022-3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26271 AN: 152026 Hom.: 2810 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26259 AN: 152144 Hom.: 2806 Cov.: 32 AF XY: 0.172 AC XY: 12821 AN XY: 74374

African (AFR) AF: 0.0651 AC: 2705 AN: 41538

American (AMR) AF: 0.155 AC: 2375 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3464

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5186

South Asian (SAS) AF: 0.144 AC: 695 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2805 AN: 10552

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16102 AN: 67982

Other (OTH) AF: 0.175 AC: 369 AN: 2114

Alfa AF: 0.209 Hom.: 10607

Bravo AF: 0.160

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Aneurysm-osteoarthritis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.98
PhyloP100		1.9
Mutation Taster		=78/22	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17293632; hg19: chr15-67442596;